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Table 4 Characteristics of pivotal studies (COMPASS)

From: Oncologic orphan drugs approved in the EU – do clinical trial data correspond with real-world effectiveness?

Drug Indication Pivotal study Primary endpoint Study phase Control Design Performance status [16] No. of patients OS effect in months QoL effect
Imatinib GIST Demetri 2002 [36]
DeMatteo 2009 [21]
ORR
RFS
II
III
Imatinib (different dose)
Placebo
Rand. OL
Rand. DB
ECOG ≤3
ECOG ≤2
147
713
n/a
n/a
NE
NE
Imatinib DFSP Heinrich 2008 [39] ORR II None Single-arm ECOG ≤2 18 NE NS
Mitotane Adrenocortical carcinoma Several pivotal studies OS, PFS, ORR n/a n/a n/a n/a > 500 n/a n/a
Sunitiniba GIST Demetri 2006 [22] TTP III Placebo Rand. DB ECOG ≤1 312 n/a NE
Sunitinib RCC Motzer 2006 [40]
Motzer 2007 [31]
ORR
PFS
II
III
None
IFN-α
Single-arm
Rand. OL
ECOG ≤1
ECOG ≤1
106
750
n/a
n/a
NE
Improved
Sorafeniba RCC Escudier 2007 [24] OS III Placebo Rand. DB ECOG ≤1 903 n/a NS
Sorafenib HCC Llovet 2008 29 OS, TTP III Placebo Rand. DB ECOG ≤2 602 2.8 NE
Sorafenib Thyroid carcinoma Brose 2014 [20] (DECISION) PFS III Placebo Rand. DB ECOG ≤2 417 n/a NS
Temsirolimus RCC Hudes 2007 [26]
(ARCC)
OS III IFN-α Rand. OL Karnofsky ≥60 (ECOG 1) 626 3.6 NS
Trabectedin STS Demetri 2009 [35] TTP II Trabectedin (different dose) Rand. OL ECOG ≤1 266 2.1 (NS) NE
Trabectedin Ovarian cancer Monk 2010 [29] PFS III Single-agent PLD Rand. OL ECOG ≤2 672 n/a NS
Mifamurtide Osteosarcoma Meyers 2005 [28] EFS III Ifosfamide Rand. OL (factorial) Not reported 678 n/a NE
Everolimusa RCC Motzer 2008 [30] PFS III Placebo Rand. DB Karnofsky ≥70 (ECOG 1) 416 n/a NS
Cabozantinib Medullary thyroid cancer Elisei 2013 [23] PFS III Placebo Rand. DB ECOG ≤2 330 n/a NE
Olaparib Ovarian cancer Ledermann 2012 [37] PFS II Placebo Rand. DB ECOG ≤2 265 n/a NS
Ramucirumab Gastric cancer Wilke 2014 [34] (RAINBOW)
Fuchs 2014 [25] (REGARD)
OS
OS
III
III
Placebo
Placebo
Rand. DB
Rand. DB
ECOG ≤1
ECOG ≤2
665
355
2.2
1.4
NS
NS
Dinutuximaba Neuroblastoma Study not yet published [19] EFS III Isotretinoin Rand. OL Karnofsky ≥50 (ECOG 2) 230 n/a NE
Lenvatinib Thyroid cancer Schlumberger 2015 [32] PFS III Placebo Rand. DB ECOG ≤3 392 n/a NE
Olaratumab STS Tap 2016 [38] PFS Ib/II Doxorubicin Rand. OL ECOG ≤2 133 11.8 NE
Nanoliposomal irinotecan Pancreatic cancer Wang-Gillam 2016 [33] OS III Fluorouracil and folinic acid Rand. OL Karnofsky ≥70(ECOG 1) 417 1.9 NS
  1. COMPASS Clinical Evidence of Orphan Medicinal Products – an ASSessment tool, DB double-blind, DFSP Dermatofibrosarcoma protuberans, ECOG Eastern Cooperative Oncology Group, EFS event-free survival, GIST gastrointestinal stromal tumor, HCC hepatocellular carcinoma, IFN-α interferon alfa, NE not evaluated, NS no significant improvement, ORR overall response rate, OS overall survival, PFS progression-free survival, PLD pegylated liposomal doxorubicin, pNET pancreatic neuroendocrine tumor, PLD pegylated liposomal doxorubicin, Rand DB randomized double-blind, Rand OL randomized open-label, RCC renal cell carcinoma, STS soft tissue sarcoma, TTP time to tumor progression
  2. a Pivotal study was terminated early